rs144468085

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012344.4(NTSR2):​c.1154G>T​(p.Arg385Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R385Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NTSR2
NM_012344.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.731
Variant links:
Genes affected
NTSR2 (HGNC:8040): (neurotensin receptor 2) The protein encoded by this gene belongs to the G protein-coupled receptor family that activate a phosphatidylinositol-calcium second messenger system. Binding and pharmacological studies demonstrate that this receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. However, unlike NT1 receptor, this gene recognizes, with high affinity, levocabastine, a histamine H1 receptor antagonist previously shown to compete with neurotensin for low-affinity binding sites in brain. These activities suggest that this receptor may be of physiological importance and that a natural agonist for the receptor may exist. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06411645).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTSR2NM_012344.4 linkc.1154G>T p.Arg385Leu missense_variant Exon 4 of 4 ENST00000306928.6 NP_036476.2 O95665

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTSR2ENST00000306928.6 linkc.1154G>T p.Arg385Leu missense_variant Exon 4 of 4 1 NM_012344.4 ENSP00000303686.5 O95665

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461878
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
2.3
DANN
Benign
0.85
DEOGEN2
Benign
0.33
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.063
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.064
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.066
Sift
Benign
0.23
T
Sift4G
Benign
0.19
T
Polyphen
0.0
B
Vest4
0.092
MutPred
0.29
Gain of ubiquitination at K384 (P = 0.0505);
MVP
0.27
MPC
0.18
ClinPred
0.24
T
GERP RS
1.9
Varity_R
0.091
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144468085; hg19: chr2-11798684; API